Bleeding Disorders in Children

Comprehensive vocabulary flashcards covering the pathophysiology, clinical features, laboratory evaluation, and management of pediatric bleeding disorders, including Vitamin K Deficiency Bleeding, Von Willebrand Disease, and Hemophilia.

Hemostasis

The active physiologic process that clots blood to arrest hemorrhage following blood vessel injury.

Bleeding

A rupture of the homeostatic equilibrium state between blood fluidity and coagulation.

Primary Hemostasis

The immediate hemostatic response comprising a vascular response (vasoconstriction) and a platelet response (platelet adhesion, activation, release of storage granules, and aggregation) to form a primary hemostatic plug.

Secondary Hemostasis

The cascade of enzymatic reactions involving coagulation factors that leads to the generation of thrombin and the stabilization of a fibrin clot.

Fibrinolysis

The enzymatic breakdown of a blood clot in which plasminogen is converted to plasmin, which lyses the fibrin clot to restore vascular integrity and produces fibrin degradation products (FDP).

Bleeding Time (BT)

A screening laboratory test that evaluates platelet function and platelet interaction with the vessel wall; it is prolonged in thrombocytopenia ($< 100{,}000/\text{mm}^3$), qualitative platelet disorders, and von Willebrand disease.

Thrombin Time (TT)

A test measuring the time required for the final step of the clotting cascade—the conversion of fibrinogen to fibrin; prolonged by reduced or dysfunctional fibrinogen or heparin use.

Prothrombin Time (PT)

A coagulation test evaluating the extrinsic and common coagulation pathways; it is the first test to become prolonged in vitamin K deficiency due to the short half-life of Factor VII.

Partial Thromboplastin Time (PTT)

A coagulation test assessing the intrinsic and common coagulation pathways; prolonged in hemophilia A and B, contact factor deficiencies, and typically corrected by mixing studies unless a specific factor inhibitor is present.

Neonatal Coagulation Factor Profile

The developmental state of hemostasis in which Factors II, VII, IX, X, and contact factors are physiologically low at birth and reach adult levels around $6\text{ months}$, while fibrinogen, Factor V, Factor VIII, VWF, and platelet counts are near normal.

Phylloquinone (Vitamin $K_1$)

The green plant-derived dietary form of vitamin K.

Menaquinone (Vitamin $K_2$)

A series of vitamin K compounds synthesized endogenously by intestinal microflora.

$\gamma$-Carboxylation of Vitamin K-Dependent Proteins

A post-translational modification catalyzed by $\gamma$-glutamyl carboxylase requiring vitamin K and $\text{CO}_2$, which converts glutamic acid residues into $\gamma$-carboxyglutamate (Gla) residues, enabling the proteins to bind calcium ($\text{Ca}^{2+}$) and achieve functional activity.

Vitamin K-Dependent Coagulation Proteins

Procoagulant factors II (prothrombin), VII, IX, and X, as well as natural anticoagulant proteins C, S, and Z.

PIVKA-II (Proteins Induced by Vitamin K Absence-II)

Undercarboxylated Factor II (prothrombin) that circulates at elevated levels in the absence of adequate vitamin K; serves as a sensitive diagnostic laboratory marker for mild vitamin K deficiency.

Classic Vitamin K Deficiency Bleeding (VKDB)

A hemorrhagic condition (formerly classic hemorrhagic disease of the newborn) presenting between $2\text{ and }7\text{ days}$ of life, accentuated by the physiologic nadir of vitamin K-dependent factors at $48\text{--}72\text{ hours}$, primarily occurring in infants not receiving prophylactic vitamin K at birth.

Very Early-Onset VKDB

Vitamin K deficiency bleeding occurring within $0\text{--}24\text{ hours}$ of birth, caused by maternal medications that cross the placenta and disrupt vitamin K metabolism (such as warfarin, phenobarbital, and phenytoin); associated with intracranial hemorrhage in $25\%$ of cases.

Late-Onset VKDB

Vitamin K deficiency bleeding presenting between $2\text{ weeks}$ and $12\text{ weeks}$ (up to $6\text{ months}$) of life; strongly linked to parental refusal of neonatal vitamin K prophylaxis combined with exclusive breastfeeding or malabsorptive states (e.g., cystic fibrosis, biliary atresia), carrying up to a $50\%$ risk of intracranial hemorrhage.

Von Willebrand Factor (VWF)

A multimeric glycoprotein synthesized in endothelial cells and megakaryocytes that binds subendothelial collagen and platelet receptor GPIb for adhesion, links platelets via GPIIb/IIIa and fibrinogen for aggregation, and acts as a protective carrier protein to prolong the half-life of Factor VIII.

Type 1 Von Willebrand Disease (VWD)

An autosomal dominant disorder characterized by a partial quantitative deficiency of VWF (diagnosed by NIH guidelines as $\text{VWF:Ag} < 30\,\text{IU/dL}$); the most common variant, accounting for $70\text{--}80\%$ of cases.

Type 2 Von Willebrand Disease (VWD)

A variant of von Willebrand disease characterized by qualitative structural or functional abnormalities of the VWF protein, inherited in an autosomal dominant or recessive pattern.

Type 3 Von Willebrand Disease (VWD)

The rarest and most severe form of VWD, inherited in an autosomal recessive manner, characterized by virtually complete absence of VWF and very low Factor VIII levels, causing severe hemophilia-like bleeds.

Ristocetin Cofactor Activity (VWF:RCo)

A functional laboratory assay that measures the ability of von Willebrand factor to interact with and agglutinate platelets in the presence of the antibiotic ristocetin.

Desmopressin (DDAVP)

A synthetic vasopressin analogue that stimulates the exocytosis of stored endogenous VWF and Factor VIII from endothelial cells; used for treating mild bleeds or preparing patients for minor surgery in mild Factor VIII hemophilia and most Type 1 VWD.

Hemophilia A

An X-linked recessive coagulopathy resulting from a deficiency of coagulation Factor VIII; represents the most common severe inherited bleeding disorder, affecting approximately $1\text{ in }5{,}000$ males and accounting for $85\%$ of hemophilia cases.

Hemophilia B

An X-linked recessive bleeding disorder caused by a deficiency of functional coagulation Factor IX (encoded on the long arm of the X chromosome).

Hemarthrosis

Bleeding into a joint cavity, which represents the hallmark and most frequent site of hemorrhage in hemophilia; initially affects the ankle in young crawling children and later commonly involves the knees and elbows.

Target Joint

A specific joint that has sustained recurrent hemarthroses, leading to synovial inflammation, chronic joint destruction, and predisposing the joint to frequent spontaneous bleeding.

Severe Hemophilia

A classification of hemophilia defined by a factor activity level of $< 1\,\text{U/dL}$ ($< 1\%$), typically presenting with frequent spontaneous hemarthroses and deep tissue hematomas in infancy or early childhood.

Moderate Hemophilia

A classification of hemophilia characterized by a factor coagulant level of $1\text{--}5\,\text{U/dL}$ ($1\text{--}5\%$), in which bleeding episodes typically follow mild trauma or minor surgical procedures.

Mild Hemophilia

A classification of hemophilia characterized by a factor coagulant level of $> 5\,\text{U/dL}$ ($> 5\%$ to $< 40\%$), in which abnormal bleeding typically manifests only following major trauma or significant surgery.

Factor Inhibitor

An neutralizing alloantibody directed against infused Factor VIII (developing in $25\text{--}35\%$ of Hemophilia A patients) or Factor IX (developing in $3\%$ of Hemophilia B patients) that prevents normal in vitro correction of PTT upon mixing with normal plasma.